This invention relates to novel processes for preparing intermediates (particularly 2-(arylhydrazino)succinonitrile compounds and 3-(arylhydrazono)propionitrile derivatives) useful in the preparation of pesticides.
European Patent Publication Nos. 0295117 and 0234119 describe the preparation of pesticidally active phenylpyrazole compounds and of 5-amino-1-aryl-3-cyanopyrazole intermediate compounds used in their synthesis.
Various methods for preparing these compounds are known. The present invention seeks to provide improved or more economical methods for the preparation of pesticides and the intermediate compounds useful in preparing them.
German Patent Publication No.3612940 discloses the preparation of 5-amino-1-arylpyrazole derivatives of general formula: 
wherein Ar represents substituted phenyl or pyridyl, which can be used as intermediates in the preparation of compounds possessing herbicidal or pesticidal properties, by the reaction of arylhydrazine hydrochloride salts with formylacetonitrile sodium salt of formula:
NaOCHxe2x95x90CHxe2x80x94CN
to give hydrazone compounds of general formula:
Arxe2x80x94NHxe2x80x94Nxe2x95x90CHxe2x80x94CH2xe2x80x94CN
wherein Ar is as hereinbefore defined; which are then cyclised in the presence of a base.
However it may be desirable to obtain the hydrazone compounds in a pure form useful for their further conversion into pesticides. Known procedures may result in the formation of hydrazones which are contaminated with the cyclised 5-amino-1-arylpyrazole product.
The present applicants have surprisingly discovered a novel process for the preparation of the hydrazone compounds without cyclisation occurring. The hydrazone compounds may then be used either to provide a new method to prepare the 5-amino-1-arylpyrazole compounds, or in a novel process which involves addition of a cyanide to provide 2-(arylhydrazino)succinonitrile derivatives which may be further processed to provide important 5-amino-1-aryl-3-cyanopyrazole compounds which are valuable intermediates for the preparation of pesticides.
U.S. Pat. No.4,824,960 describes the preparation of 5-amino-1-arylpyrazole derivatives of general formula: 
wherein Ar represents substituted phenyl or pyridyl, which can be used as intermediates in the preparation of compounds possessing herbicidal or pesticidal properties, by the reaction of arylhydrazines of formula:
Arxe2x80x94NHxe2x80x94NH2
wherein Ar is as hereinbefore defined, with acrylonitrile of formula:
NCxe2x80x94CHxe2x95x90CH2
in a first stage in the presence of a diluent and optionally a catalyst to give the 3-arylhydrazinopropionoitrile compounds of formula:
Arxe2x80x94NHxe2x80x94NH-CH2-CH2xe2x80x94CN
wherein Ar is as hereinbefore defined, followed by oxidation and cyclisation in a second process stage.
However if it is desired to perform an oxidation of the above 3-arylhydrazinopropilonitriles (without cyclisation to the 5-amino-1-arylpyrazoles) in order to obtain 3-arlylhydrazonopropionitriles, which may then be further processed to provide important 5-amino-1-aryl-3-cyanopyrazole compounds which are valuable intermediates in the preparation of pesticides, a different process must be employed.
The present invention accordingly provides a process (A) for the preparation of a compound of formula (I): 
wherein W represents nitrogen or xe2x80x94CR3;
R1 represents halogen, haloalkyl (preferably trifluoromethyl), haloalkoxy (preferably trifluoromethoxy), R4S(O)nxe2x80x94, or SF5;
R2 represents hydrogen or halogen (for example chlorine or bromine);
R3 represents halogen (for example chlorine or bromine);
R4 represents alkyl or haloalkyl; and
n represents 0,1 or 2; which process comprises the reaction of a compound of formula (II): 
xe2x80x83wherein R5 and R6 independently represent alkyl or together represent an alkylene chain containing two or three carbon atoms, with an acid addition salt of an arylhydrazine compound of formula (III): 
xe2x80x83wherein R1, R2 and W are as hereinbefore defined. Compounds of formula (I) may exist as a mixture of syn and anti isomers or as individual isomers.
Unless otherwise specified in the present specification xe2x80x98alkylxe2x80x99 means straight- or branched-chain alkyl having from one to six carbon atoms (preferably one to three). Unless otherwise specified xe2x80x98haloalkylxe2x80x99 and xe2x80x98haloalkoxyxe2x80x99 are straight- or branched-chain alkyl or alkoxy respectively having from one to six carbon atoms (preferably one to three) substituted by one or more halogen atoms selected from fluorine, chlorine or bromine.
Generally R5 and R6 in formula (II) represent the same alkyl group, preferably methyl or ethyl.
The acid addition salts of the compounds of formula (III) are preferably the salts formed from strong acids such as mineral acids, for example sulphuric acid, or preferably hydrochloric acid. Generally the salts are pre-formed but may optionally be generated in situ. The reaction may be conducted in a polar or a non-polar solvent in the presence of water. Examples of polar solvents include water; alcohols such as methanol or ethanol; nitriles such as acetonitrile; N-methylpyrrolidone or sulphoxides such as dimethyl sulphoxide. Examples of non-polar solvents include chlorinated hydrocarbons, preferably carbon tetrachloride; and hydrocarbons such as cyclohexane. The reaction temperature is generally from 20xc2x0 C. to 100xc2x0 C., preferably from 50xc2x0 C. to 90xc2x0 C. Equimolar amounts of the compounds of formula (II) and (III) are generally employed. The amount of water which may be present is from a catalytic amount to a large excess.
In formulae (I), (III) and in the formulae depicted hereinafter, preferred values of the symbols are as follows:
R1 represents haloalkyl (preferably trifluoromethyl), haloalkoxy (preferably trifluoromethoxy) or xe2x80x94SF5;
W represents xe2x80x94CR3; and R3 represents halogen;
A most preferred compound of formula (I) is 3-(2,6-dichloro-4-trifluoromethylphenylhydrazono)propionitrile.
A further preferred compound of formula (I) is 3-(2-chloro-4-trifluoromethylphenylhydrazono)propionitrile.
Compounds of formula (II) and (III) are generally known in the literature.
The process of the invention is characterised by a number of advantages. Thus, it seeks to enable 3-arylhydrazono-propionitrile compounds of formula (I) to be obtained in high yield from readily available starting materials. Furthermore the reaction can be very simple and economical to perform, and product isolation is very straightforward. Furthermore the compounds of formula (I) can be obtained without substantial cyclisation occurring.
According to a further feature of the present invention there is provided a process (B) for the preparation of a compound of formula (I), wherein W, R1 and R2 are as hereinbefore defined, which comprises the reaction of a compound of formula (IV): 
wherein R7 represents alkyl (preferably methyl or ethyl), with a compound of formula (III), wherein R1, R2 and W are as hereinbefore defined. The reaction conditions which are generally employed are the same as those used for the above preparation of a compound of formula (I) from the reaction of a compound of formula (II) with an acid addition salt of a compound of formula (III).
Compounds of formula (IV) are generally known in the literature.
According to a further feature of the present invention there is provided a process (C) for the preparation of a compound of formula (I) wherein W, R1 and R2 are as hereinbefore defined; which process comprises the oxidation of a compound of formula (V): 
wherein R1, R2 and W are as hereinbefore defined.
Suitable oxidants for the above reaction to form compounds of formula (I) include quinones such as benzoquinone, peroxides such as hydrogen peroxide, hypohalites such as sodium hypochlorite; or preferably a metal salt or oxide for example cupric chloride or mercuric oxide. The oxidation is generally conducted in a solvent. Solvents suitable for use include aromatic halogenated or non-halogenated hydrocarbons such as toluene or chlorobenzene, nitrites such as acetonitrile or amides such as N,N-dimethylformamide. The reaction temperature is generally from about 20xc2x0 C. to about 150xc2x0 C., and preferably from about 50xc2x0 C. to about 100xc2x0 C.
The molar ratio of oxidant to compound of formula (V) is generally from 0.01:1 to 5:1, preferably from 1:1 to 3:1.
According to a further feature of the present invention there is provided a process (D) for the preparation of a compound of formula (VI): 
wherein R1, R2 and W are as hereinbefore defined; which process comprises the reaction of a compound of formula (I) wherein R1, R2 and W are as hereinbefore defined, with a source of hydrogen cyanide. Compounds of formula (VI) may exist in the R- and S- forms or as mixtures thereof.
The source of hydrogen cyanide may be hydrogen cyanide gas itself, when the reaction is optionally performed in the presence of a base, for example pyridine; but it is preferably prepared in situ (to avoid the direct use of hydrogen cyanide) from a metal cyanide salt (generally an alkali metal cyanide, for example sodium cyanide or potassium cyanide),in the presence of an acid. Suitable acids include organic acids such as aliphatic carboxylic acids for example acetic acid, or halogenated aliphatic carboxylic acids for example chloroacetic acid or trifluoroacetic acid; sulphonic acids such as benzenesulphonic acid, 4-toluenesulphonic acid or methanesulphonic acid; or inorganic acids such as hydrochloric acid or sulphuric acid.
Alternative sources of hydrogen cyanide (which may be generated in situ) are trimethylsilylcyanide in water, or a mixture of trimethylsilylcyanide and a Lewis acid, for example tin (IV) tetrachloride, in a solvent such as dichloromethane or tetrahydrofuran, at a temperature of from 20xc2x0 C. to 100xc2x0 C., preferably from 30xc2x0 C to 60xc2x0 C. The reaction is preferably performed under increased pressure which increases the speed of the reaction.
The preparation of compounds of formula (VI) from compounds of formula (I) may be effected in a polar or a non-polar solvent. Examples of polar solvents which may be used include water; alcohols such as methanol or ethanol; N,N-dimethylformamide; dimethylsulphoxide; or alkanoic acids such as acetic acid. Examples of non-polar solvents include hydrocarbons such as hexane, or ethers such as tetrahydrofuran, dioxane or dialkyl ethers such as diethyl ether; or nitrites such as acetonitrile. When a metal cyanide salt is used in the presence of an acid, the preferred solvent is water or a mixture of water with a water miscible solvent. An equimolar amount or excess of the cyanide source may be employed, generally from 1 to 4 molar equivalents are used. The reaction temperature is generally from 0xc2x0 C. to 100xc2x0 C., preferably from 20xc2x0 C. to 50xc2x0 C.
Most preferably the compound of formula (VI) is 2-(2,6-dichloro-4-trifluoromethylphenylhydrazino)succinonitrile.
A further preferred compound of formula (VI) is 2-(2-chloro-4-trifluoromethylphenylhydrazino)succinonitrile.
According to a further feature of the invention processes (A) and (D) can be combined to prepare a compound of formula (VI) from a compound of formula (III).
According to a further feature of the invention processes (B) and (D) can be combined to prepare a compound of formula (VI) from a compound of formula (III).
According to a further feature of the invention processes (C) and (D) can be combined to prepare a compound of formula (VI) from a compound of formula (V).
According to a further feature of the invention the above combination of processes (C) and (D) can be combined with an additional process step (E), which comprises the reaction of an arylhydrazine compound of formula (III) wherein R1, R2 and W are as hereinbefore defined; with acrylonitrile of formula (VII):
NCxe2x80x94CHxe2x95x90CH2xe2x80x83xe2x80x83(VII)
to give a compound of formula (V) as defined above.
Compounds of formula (VII) are known.
The compounds of formula (I) obtained by process (A) or (B) or (C) of the invention may be used in the preparation of pesticidally active 5-amino-1-arylpyrazole derivatives of formula (VIII) according to the following reaction scheme: 
wherein R1, R2 and W are as hereinbefore defined.
The compounds of formula (VI) obtained by the process (D) of the invention are particularly useful in the preparation of pesticidally active 5-amino-1-aryl-3-cyanopyrazole derivatives of formula (IX) obtained from intermediate compounds of formula (X) and (XI) according to the following reaction scheme: 
wherein R1, R2 and W are as hereinbefore defined.
Compounds of formula (X) may be prepared by the oxidation of compounds of formula (VI). Suitable oxidants for the reaction include quinones such as benzoquinone, peroxides such as hydrogen peroxide, hypohalites such as sodium hypochlorite, or an alkali metal hydroxide such as sodium hydroxide in the presence of air, or preferably a metal salt or oxide for example cupric chloride or mercuric oxide. The reaction is generally conducted in a solvent. Solvents suitable for use include aromatic halogenated or non-halogenated hydrocarbons such as toluene or chlorobenzene, nitrites such as acetonitrile or amides such as N,N-dimethylformamide. The reaction temperature is generally from about 20 to about 150xc2x0 C., and preferably from about 50 to about 100xc2x0 C. The molar ratio of oxidant to compound of formula (VI) is generally from 0.01:1 to 5:1, preferably from 1:1 to 3:1.
Compounds of formula (XI) may be prepared from compounds of formula (X) according to known methods.